What's new?

The authors of this study previously identified the endosulfatase gene HSulf-1 as a down-regulated gene in ovarian cancer. In this study, and for the first time, they provide direct evidence of the critical role of HSulf-1 loss in promoting the tumorigenesis of ovarian cancer in a nude mice model. The in vitro and in vivo data also reveal a novel link between the expression of HSulf-1 and the important pro-apoptotic factor Bim. The study thus demonstrated that blocking Bim by loss of HSulf-1 expression may represent a new mechanism employed by some ovarian cancer cells to acquire higher tumorigenic ability.

What's new?

Zinc Finger Protein X-linked gene (ZFX) is a member of Zfy family of transcriptional regulators that is often highly expressed in embryonic and hematopoietic stem cells. In this study, the authors find that ZFX is commonly overexpressed in hepatocellular carcinoma, where it promotes the expression of stem cell-associated transcription factors such as Nanog and SOX-2. These findings may shed new light on chemoresistance and frequent recurrence of hepatocellular carcinomas, symptoms attributed to stemness and pluripotent behavior of this cancer.

What's new?

Dozens of proteins work together to keep cell proliferation and other functions running smoothly. Altering one protein's expression impacts many other molecules, and discovering how they interact can suggest strategies for righting the disrupted cellular processes that cause cancer. Sporadic colorectal cancer frequently involves deactivation of the APC gene, which leads to loss of regulation of the protein beta-catenin. In this study, the authors investigated a target of beta-catenin called TNFRSF19, a member of the tumor necrosis factor receptor superfamily. They discovered that TNFRSF19 is overexpressed in colorectal cancers, and that it activates NF-kB signaling. Identifying this link between β-catenin and NF-kB signaling implies a pathway by which loss of control over beta-catenin could lead to cancer, as NF-kB is well known for its regulatory role in cell proliferation.

What's new?

Precise molecular mechanisms for the altered expression of microRNAs in lung cancer are unclear. Here, the authors analyzed microRNA expression in a large sample set of lung adenocarcinomas and corresponding normal lung tissue. They identified several aberrantly expressed microRNAs that discriminate lung adenocarcinomas from normal tissue and are thus potential biomarkers for early detection. They found microRNAs differentially expressed between EGFR-mutated and EGFR wild-type lung adenocarcinomas, suggesting that microRNAs can be used as molecular biomarkers in classification. Moreover, miR-500a* expression was associated with time to progression. This study suggests that microRNA expression can be used as biomarkers for clinical course.

What's new?

Long-term survival of more than 3 years after the diagnosis of glioblastoma is a rare and poorly understood phenomenon. Here, the authors sought to elucidate the molecular aberrations in glioblastomas of long-term survivors. They demonstrate that gene expression changes and genomic imbalances in glioblastomas from long-term survivors are closely associated with IDH1/2 mutation, but not with IDH1/2-independent long-term survival. Moreover, they disclose that most gene signatures previously linked to long-term survival are indeed associated with IDH1/2 mutation and are not prognostic in patients with IDH1/2-wildtype tumors. The molecular basis of long-term survival with IDH1/2-wildtype glioblastoma remains to be resolved.

What's new?

NK cells can attack and kill tumor cells, but often tumors protect themselves. In this paper, the authors sought to uncover what was holding back the NK cells in renal cell carcinoma. They discovered that the NK cells are inhibited by too much diacylglycerol kinase and insuffficient ERK pathway activation. By restraining DGK-alpha or reactivating the ERK pathway by other means, the authors restored the activity of the NK cells, suggesting this might be a useful strategy to improve antitumor immunotherapies.

What's new?

The cancer-testis antigens are a group of unrelated proteins aberrantly expressed in various cancers. Patterns of antigen expression may potentially provide correlates of specific cancer types and disease progression. This study presents a novel microarray platform for high-throughput quantitation of anti-cancer-testis antigen autoantibody profiles in patient sera. Exploiting the higher affinity of autoantibodies, and optimized surface engineering to minimize non-specific signal, the authors achieved linearity of response and a pg/ml quantitation limit. They illustrated the utility of the method by monitoring patient response to an experimental cancer vaccine, finding evidence of differential expression and epitope utilization, and of determinant spreading.

What's New?

Ectopic metabotropic glutamate 1 (mGlu1) receptor has demonstrated oncogenic activity and is becoming an important target for personalized diagnosis and treatment strategies for melanomas. Here, for the first time, the authors have developed a positron emission tomography (PET) imaging platform in order to analyze the presence of the oncoprotein mGlu1 in melanomas, using a novel mGlu1-specific radioprobe called ¹⁸F-FITM. The ¹⁸F-FITM imaging platform has great potential for specific detection of mGlu1-positive tumors and noninvasive quantification of mGlu1 expression, and may thus help advance personalized diagnosis and treatment for patients with melanoma.

What's new?

Abnormal vaginal bleeding is a common symptom that often plagues postmenopausal women and in some cases might signal the development of endometrial cancer. The authors propose the development of a molecular test that could aid in the clinical management of vaginal bleeding. They identified eight genes for which methylation status significantly differed between endometrial carcinoma and normal endometrium. In endometrial brushings from an independent study, the candidate markers successfully discriminated between cancerous and noncancerous cells, indicating that DNA methylation biomarkers may join conventional methods in distinguishing women with endometrial carcinoma from the majority of women with benign postmenopausal bleeding.

What's new?

Some studies have concluded that non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of cancer, but women have been under-represented in these reports. In this large, prospective study of almost 130,000 postmenopausal women, the authors found that NSAIDs were associated with a reduced risk of colorectal cancer, and possibly of ovarian cancer and melanoma; however, they did not appear to reduce total cancer risk among women. These findings challenge previous assertions that NSAID use reduces overall cancer risk for women.

What's new?

Adherence to a “Mediterranean Diet” is associated with significant improvements in health status, including a lower overall risk of cancer. In this meta-analysis, the authors examined the impact of this type of diet on risks for specific types of cancer, as well as overall risk. They found that high adherence to a Mediterranean diet is associated with a significant reduction in the risk of several types of cancer, especially colorectal and aerodigestive cancers.

What's New?

In breast cancer, expression of the COX-2 gene means worse prognosis, and inhibiting COX-2 improves survival. But how does estrogen receptor (ER) figure into this? Could COX-2 expression affect tumors differently depending on ER status? Some evidence suggests that COX-2 spurs ER-negative tumors more than ER-positive ones. This team investigated the relationship between a patient's response to breast cancer treatment and COX2 genotype, ER status, and breast volume. They identified two subgroups of patients that responded poorly to treatment; knowing a patient's COX-2 genotype in concert with ER status and breast volume could help clinicians personalize treatment for higher risk individuals.

What's new?

Cervical cancer kills thousands of women every year, but early screening programs could avert many of these deaths. In this study, the authors explored whether a self-administered HPV test could improve cancer screening in sub-Saharan Africa. They compared the results from the self-collected samples with those collected by physicians, and both methods returned similar rates of HPV positivity. Self-screening, followed up with triage testing to identify high-risk lesions, could provide a practical way to screen large numbers of women and only administer further testing to HPV-positive women.

What's new?

Lung cancer is the most common cause of cancer death worldwide, and it's often caused by smoking tobacco. Even if you only count people who have never smoked, lung cancer would still rank seventh, in part because of exposure to environmental tobacco smoke. This study sought to tease out how secondhand smoke affected risk of each different lung cancer type. By pooling data from 18 case-control studies, the authors determined that exposure to secondhand smoke increased the risk of small-cell lung cancer more than any other type.

What's New?

Diagnosis of cervical cancer often occurs in women who do not participate in screening programs or visit less frequently than recommended. This Norwegian study quantifies the value of improving failures in current cervical cancer screening practices. The study demonstrates that the largest gains in health involve improvements in participation among women lost to follow-up after an abnormal test result, as well as recruiting previously unscreened women, underscoring the benefit of allocating public funds to the targeted strengthening of participation and adherence of women to existing screening programs.

What's New?

Evidence suggests that milk intake may decrease the risk of colorectal cancer (CRC). In this meta-analysis, the authors found that calcium is responsible for this protective effect, and that the dose-response curve is virtually linear within the observed range. They also compared dietary with supplemental calcium intake, and found that both sources provide similar benefits. These results suggest that even people who are lactose intolerant or consume low levels of dairy products may still reduce their risk of CRC by taking calcium in the form of supplements and non-dairy foods.

What's new?

Both general and abdominal obesity are associated with an increased risk of developing colorectal cancer (CRC), but whether one or both types of obesity affect survival in CRC has been unclear. In this study, the authors found that, indeed, each type of fat was independently associated with an increased risk for CRC-specific and all-cause death. However, CRC patients with both types of obesity had the highest risk of death. These results underline the importance of maintaining a healthy weight throughout life.

What's new?

While metastatic breast cancer remains incurable, metastatic triple-negative breast cancer (mTNBC) is proving particularly challenging because tumors lack recognized therapeutic molecular biology targets. This report is the first clinical phase II study of a highly potent inhibitor of VEGFR2 (apatinib) in mTNBC, evaluating its activity and safety. The results indicate that apatinib daily dose of 500mg rather than 750mg is the recommended starting dose for heavily pretreated mTNBC patients in China, with measurable and encouraging rates of partial response and progression-free survival. In addition, tumor pVEGFR2 expression shows promise as an apatinib efficacy predictor of mTNBC, which warrants further validation.

What's New?

Occupational asbestos exposure is thought to be a possible risk factor for esophageal, gastric, and colorectal cancers, but evidence for an association is limited. In this prospective population-based cohort study, (prolonged) exposure to high levels of asbestos was found to be associated with overall gastric cancer, esophageal adenocarcinoma, gastric non-cardia adenocarcinoma (GNCA), total and distal colon cancer, and rectal cancer risk. While the risk of overall gastric cancer and GNCA risk was further associated with lower levels of asbestos exposure, statistical significance for lower-level exposure was lost following adjustment for potential confounders, particularly smoking.

What's new?

What if a cancer could reveal early on whether it was headed for metastasis? These authors tried to find out whether circulating tumor cells in bladder cancer patients could predict whether the cancer would recur and spread. They found circulating tumor cells in 20% of patients with stage I bladder cancer, and the presence of these cells predicted shorter time to recurrence and time to progression, suggesting that testing for CTCs could identify patients who would benefit from systemic treatment right from the start.

What's new?

Both anti-tumor and pro-angiogenic responses are produced from the interaction of CD40 and CD40L, making for an intriguing duality in tumor biology. However, the possibility that pro-angiogenic responses generated through the induction of vascular endothelial growth factor (VEGF) expression self-limit anti-tumor responses also poses unique therapeutic challenges. Here, in an established mouse tumor model, simultaneous augmentation of the CD40-induced anti-tumor immune response and neutralization of CD40-induced VEGF production was found to enhance the anti-tumor function of CD40. The combined use of an agonistic anti-CD40 antibody and a neutralizing anti-VEGF antibody represents a possible anti-tumor strategy for the clinic.